Neisseria meningitidis is a causative agent of bacterial meningitis and sepsis. Meningococcal disease annually causes an estimated 500,000 cases and 50,000 deaths worldwide (Plested et al., 2001). Serologically, N. meningitidis are separated into different antigenic groups based on the structure of their outer membrane protein (e.g., serotype class 2/3 outer membrane protein), their capsular polysaccharide (e.g., serogroups A, B, C, Y, W-135, X, Y, Z and 29E) and their lipo-oligosaccharide (e.g., immunotypes L1-L12).
N. meningitidis serogroups A, B, and C are responsible for approximately ninety percent of cases of meningococcal meningitis. Among N. meningitidis strains, at least twelve lipo-oligosaccharide (LOS) immunotypes (L1-L12) have been identified. The L1-L7 immunotypes are exclusively associated with group B and C meningococci, whereas the L10-L12 immunotypes are associated with group A meningococci. Only two immunotypes, L8 and L9, overlap between the groups. The most frequent LOS immunotypes among clinical isolates are L2, L3, L4, and L7 in North America (Zollinger and Mandrell, 1977) and L1, L2, L3, L7 and L9 in Europe (Verheul et al., 1993a) (e.g., ninety five percent of the N. meningitidis isolates in Norwegian patients expressed the L3,7,9 immunotype (Anderson et al., 1997)).
Success in the prevention of group A, C, Y, and W-135 meningococcal meningitis in certain age groups has been achieved using monovalent and multivalent polysaccharide immunogenic compositions. However, serogroup A, C, W-135 and Y capsular polysaccharide compositions are generally not effective in children less than two years of age, the population most at risk of meningococcal disease.
N. meningitidis group B accounts for approximately fifty percent of bacterial meningitis in infants and children residing in the U.S. and Europe. In adolescents, experimental N. meningitidis group B immunogenic compositions consisting of outer membrane protein vesicles have been found to be approximately fifty percent protective. However, no protection has been observed when these outer membrane protein vesicles are administered to infants and children, the age groups at greatest risk of meningococcal disease.
Further complicating the development of immunogenic composition against N. meningitidis is the high inter-strain and intra-strain variation in the LOS outer core structure, thereby resulting in extensive antigenic diversity and poor immunogenicity. For example, phase variation can produce heterogeneous oligosaccharide chains, thereby changing the antigenic profile of N. meningitidis strains. Furthermore, the terminal galactose residue of the oligosaccharide (OS) outer core structure of most N. meningitidis immunotypes comprises a lacto-N-tetraose unit which mimics certain human blood group antigens (Mandrel et al., 1988), potentially reducing immunogenicity and/or inducing an autoimmune response.
Thus, there is currently a need in the art for immunogenic compositions which can elicit immune responses against the predominant Neisseria meningitidis serogroups A, B, C, Y and/or W-135.